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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-08-24 to 1988-09-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): o-Chloraniline
- Physical state: yellow-orange, clear liquid
- Analytical purity: 99.6 % (IR spectroscopy)
- Impurities (identity and concentrations):
<0.01 % cyclohexylamine
<0.01 % N-isopropylaniline
<0.01 % 2-chloro-N-Isopropylanilin
0.08% aniline
<0.01% 2-Isopropylaniline
<0.01% o-nitrochlorobenzene
0.24% p-chloroaniline
<0.01% m-chloroaniline
<0.01% 2,4-dichloroaniline
<0.01% 2,5-dichloroaniline
<0.01% 2,3-dichloroaniline
<0.01% 2,3-dichloroaniline
<0.01% o-phenylendiamine
0.03 % unknown impurities
- Purity test date: 1 Feb 1988
- Lot/batch No.: Lagerkessel 15/ 594 488
- Stability under test conditions: stable throughout the test period
- Storage condition of test material: room temperature, dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: 2-3 months
- Weight at study initiation: 170-210 g
- Fasting period before study:
- Housing: 5 per macrolon III cage, changed every week, animals marked individually,
- Bedding: wood chips Type S8/15 Ssniff
- Diet : ad libitum; Altromin 1324
- Water: ad libitum; tap water
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12, artificial 14 W/m²

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: from Rhema Labortechnik, Hofheim, Germany
- Exposure chamber volume: 7 L
- Method of holding animals in test chamber: animals were held in place in special test tubes
- Source and rate of air: 10 L/ min; about 85 air changes /h
- Method of conditioning air: air was led through a bottle with prewarmed test substance
- System of generating particulates/aerosols: two-component jet and conditioned compressed air (480 kPa) were used to nebulize liquid test substance in the baffle
- Method of particle size determination: aerodynamic particle sizer with laser-velocimeter (TSI-APS 3300)
- Treatment of exhaust air: 70 % of the incoming air were withdrawn as exhaust air
- Temperature, humidity, pressure in air chamber:
aerosol: T= 20-22°C
Humidity=34 %
vapour: T= 20-22°C
Humidity= 32 %-35 % (group 2 and 3); 55 % (group 4)

TEST ATMOSPHERE (vapour)
- Brief description of analytical method used: Ratfisch RS 55 with FI detector
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (aerosol)
- Brief description of analytical method used: not possible due to condensation


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 37 to 44 % <5 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
group 5: 5.53 µm/ 1.81
group 6: 6.11 µm/ 1.81

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
analytical, vapour: 0.371, 0.745 or 1.156 mg/L, group 2,3 and 4, respectively
analytical, aerosol: 2.642 or 4.406 mg/L (maximal attainable dose), group 5 and 6, respectively
No. of animals per sex per dose:
5 per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed twice a day (including weekends, not during actual exposure period), weighed before the test and on day 3, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
body weight: ANOVA [F-test:Box-test; if different Tukey-Kramer test with Howell modification]
necroscopy: Chi-Square test and pairwise Fisher's test

Results and discussion

Preliminary study:
no
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.406 mg/L air
Exp. duration:
4 h
Mortality:
no mortality observed
Clinical signs:
other: no signs of toxicity were observed in group 1 to 3 (up to 0.745 mg/L) group 4, 5 and 6 displayed following signs of toxicity: group 4 (11.556 mg/L, vapour): tremor (4 h-4 h) group 5 (26.421 mg/L, aerosol): reduced motor activity, tremor, face down positio
Body weight:
male rats of group 4, 5 and 6 and female rats of group 6 displayed delayed body weight gain on day 3
Gross pathology:
no pathophysiological changes were observed

Any other information on results incl. tables

Only slight symptoms of an irritating potential for respiratory organs (nasal secretion) at 4.4 mg/L (aerosol).

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information T, R25 Criteria used for interpretation of results: EU
Conclusions:
Like other chloroanilines, the primary toxic effect of 2-chloroaniline is methaemoglobin
formation. Taking into account that humans are much more sensitive to methaemoglobin
producing substances than rats 2-chloroaniline is classified in Toxicity Category III.
Executive summary:

Märtins, T (1990)

2 -chloroaniline was tested for acute inhalation toxicity according to OECD 403 on male and female young adult wistar rats in a head/nose only apparatus for 4 h. The concentration in the test chamber was monitored throughout the experiment. Following concentration (analytical) of 2 -chloroaniline were applied as vapour: 0.371, 0.745 or 1.156 mg/L (group 2,3 and 4, respectively) and as aerosol up to the maximal attainable dose: 2.642 or 4.406 mg/L, group 5 and 6, respectively. Controls were exposed in the same way to a water/air mixture.No mortality was observed in all groups. No pathophysiological changes were evident. Signs of toxicity were only observed in Group 4 to 6 and included: tremor, face down position, reduced mortor activity and in the highest dose group serous secretion from the nose, indicating an irritating effect to the respiratory system. Therefore the LD50 value is greater than 4.406 mg/L. Based on this study o-Chloroaniline showed only slight toxic potential without mortality and should be classified as harmul if inhaled.